FOXG1 Enhances Paclitaxel Resistance in Prostate Cancer via NANOG-Mediated Cellular Stemness
Chong Shen, Yu Ren, Xiangrong Ying, Gangfeng Wu, Chuanchuan Zhan, Zhengang Luo, Shuixiang Tao, Haojie ZhangBackground
Paclitaxel (PTX) is an effective chemotherapeutic agent for prostate cancer (PCa), yet resistance emerges with disease progression. Cancer-cell stemness is intimately linked to PTX resistance. This work clarifies whether FOXG1 modulates PTX resistance in PCa via cellular stemness.
Methods
TCGA database was interrogated for FOXG1 expression in PCa. PTX-resistant PCa cell lines were generated by stepwise escalation of PTX concentration. qRT-PCR quantified FOXG1 and NANOG levels in PCa cells. CCK-8, sphere-formation assay, and flow cytometry evaluated cell viability, stemness, and apoptosis, respectively. Western blot assessed apoptosis-related proteins. JASPAR predicted FOXG1 binding sites within NANOG. Dual-luciferase reporter and ChIP verified FOXG1–NANOG interaction.
Results
Bioinformatic analysis revealed elevated FOXG1 expression in PCa tissues. FOXG1 levels were likewise increased in PCa cells. A PTX-resistant PC-3 sub-line (PC-3-R) was established. FOXG1 silencing suppressed stemness and viability of PC-3-R cells under PTX exposure while promoting apoptosis. FOXG1 was identified as an upstream regulator of NANOG. NANOG overexpression reversed the effects conferred by FOXG1 silencing on PC-3-R cells.
Conclusion
FOXG1 fosters NANOG-mediated cellular stemness to potentiate PTX resistance in PCa.